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A phase 1b randomized clinical trial of CT1812 to measure Aβoligomer displacement in Alzheimer’s disease using an indwelling CSF catheter

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Translational Neurodegeneration 2023年第1期12卷 568-571页

作者： Kelsie m.LaBarbera Yvette I.Sheline Nicholas J.Izzo Carla m.Yuede Lora Waybright Raymond Yurko Hannah m.Edwards Woodrow D.Gardiner Kaj Blennow Henrik Zetterberg Anne Börjesson-Hanson Roger morgan Charles S.Davis Robert J.Guttendorf Lon S.Schneider Steven DeKosky Harry LeVine III michael Grundman Anthony O.Caggiano John R.Cirrito susan m.catalano mary E.Hamby Cognition Therapeutics Inc. PittsburghPAUSA University of Pennsylvania PhiladelphiaUSA Washington University St.LouisUSA University of Gothenburg MölndalSweden Department of Psychiatry and Neurochemistry Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at the University of GothenburgMölndalSweden Clinical Neurochemistry Laboratory Sahlgrenska University HospitalMölndalSweden Department of Neurodegenerative Disease UCL Institute of NeurologyQueen SquareLondonUK UK Dementia Research Institute at UCL LondonUK Hong Kong Center for Neurodegenerative Diseases Clear Water BayHong KongChina Wisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonWIUSA Karolinska University Hospital StockholmSweden medSurgPI LLCRaleighNCUSA CSD Biostatistics Inc.Oro ValleyAZUSA Aclairo Pharmaceutical Development Group IncViennaVAUSA Keck School of medicine of USC Los AngelesCAUSA mcKnight Brain Institute University of FloridaGainesvilleFLUSA Sanders-Brown Center on Aging University of KentuckyLexingtonKYUSA Global R&D Partners LLCSan DiegoCAUSA Department of Neurosciences University of CaliforniaSan DiegoUSA

Trial Registration:may 11th,2018 *** Identifier:NCT03522129 https://clini caltr ***/ct2/show/*** therapies for Alzheimer’s disease(AD)target a wide range of mechanisms,yet promising dis-ease-modifying therapies remain a huge unmet *** evidence indicates that the oligomeric form of amyloid-beta(Aβ)is a toxic species contributing to AD through synaptic damage and neuronal toxicity[1].

关键词： Alzheimer Aβ damage

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Current and near-term advances in Earth observation for ecological applications

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Ecological Processes 2021年第1期10卷 1-57页

作者： susan L.Ustin Elizabeth m.middleton John muir Institute of the Environment University of CaliforniaDavisCA 95616USA NASA/Goddard Space Flight Center(Emerita) GreenbeltMD 20771USA.

There is an unprecedented array of new satellite technologies with capabilities for advancing our understanding of ecological processes and the changing composition of the Earth’s biosphere at scales from local plots to the whole *** identified 48 instruments and 13 platforms with multiple instruments that are of broad interest to the environmental sciences that either collected data in the 2000s,were recently launched,or are planned for launch in this *** have restricted our review to instruments that primarily observe terrestrial landscapes or coastal margins and are available under free and open data *** focused on imagers that passively measure wavelengths in the reflected solar and emitted thermal *** suite of instruments we describe measure land surface characteristics,including land cover,but provide a more detailed monitoring of ecosystems,plant communities,and even some species then possible from historic *** newer instruments have potential to greatly improve our understanding of ecosystem functional relationships among plant traits like leaf mass area(LmA),total nitrogen content,and leaf area index(LAI).They provide new information on physiological processes related to photosynthesis,transpiration and respiration,and stress detection,including capabilities to measure key plant and soil biophysical *** include canopy and soil temperature and emissivity,chlorophyll fluorescence,and biogeochemical contents like photosynthetic pigments(e.g.,chlorophylls,carotenoids,and phycobiliproteins from cyanobacteria),water,cellulose,lignin,and nitrogen in foliar *** data will enable us to quantify and characterize various soil properties such as iron content,several types of soil clays,organic matter,and other *** of these satellites are in low Earth orbit(LEO),but we include a few in geostationary orbit(GEO)because of their potential to measure plant physiological traits over diurnal periods,impro

关键词： Terrestrial ecosystems Earth Observing Satellites Ecosystem processes Physiological functions multispectral Hyperspectral Thermal LiDAR Radar imagers Biochemistry Soil properties Species mapping Change detection 3D canopy structure Topography

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ASSESSING THE LINK BETWEEN PUBLIC OPINION AND SOCIAL SUSTAINABILITY IN BUILDING AND INFRASTRUCTURE PROJECTS

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Journal of Green Building 2015年第3期10卷 177-190页

作者： Vanessa Valentin susan m.Bogus Department of Civil Engineering University of New MexicoAlbuquerqueNM 87131USA

Increasing the use of social sustainability in the decision-making process for build-ing and infrastructure projects requires that it be defined such that it can be evaluated *** potential indicator of social sustainability in infrastruc-ture projects is public opinion,which can provide a means to evaluate the level of social sustainability on a project based on personal *** opinion includes both support and opposition for a *** this study,the causes or triggers for public opposition to a construction project are identified and then compared to principles of social sustainability to determine if they are *** case study projects were used to identify common triggers of public *** results suggest that common triggers of public opposition are related to land acquisition,escalating construction costs and the presence of endangered species on the project *** of the twelve principles of social sustainability that were identified were determined to be related to public *** results of this study suggest that public opposition could be used as a measure for some elements of social sus-tainability but that further research into other measures for social sustainability is necessary.

关键词： social sustainability public opinion triggers of public opposition to building and infrastructure projects

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Biased activity of soluble guanylyl cyclase:the Janus face of thymoquinone

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Acta Pharmaceutica Sinica B 2017年第4期7卷 401-408页

作者： Charlotte Detremmerie Paul m.Vanhoutte susan Leung Department of Pharmacology and Pharmacy and State Key Laboratory for Pharmaceutical Biotechnology Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina

The natural compound thymoquinone, extracted from Nigella sativa(black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endotheliumindependent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously,thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase(sGC) producing inosine 3',5'-cyclic monophosphate(cyclic ImP) rather than guanosine 3',5'-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic ImP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

关键词： Thymoquinone Endothelium-dependentcontraction Nitric oxide Soluble guanylyl cyclase Cyclic ImP NADPH:quinone oxidoreductase

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Social learning in nest-building birds watching live-streaming video demonstrators

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Integrative Zoology 2019年第2期14卷 204-213页

作者： Lauren m.GUILLETTE susan D.HEALY School of Biology University of St AndrewsSt AndrewsFifeUK

Determining the role that social learning plays in construction behaviors,such as nest building or tool manufacture,could be improved if more experimental control could be gained over the exact public information that is provided by the demonstrator,to the observing *** video playback allows the experimenter to choose what information is provided but will only be useful in determining the role of social learning if observers attend to,and learn from,videos in a manner that is similar to live *** goal of the current experiment was to test whether live-streamed video presentations of nest building by zebra finches Taeniopygia guttata would lead observers to copy the material choice demonstrated to ***,males that had not previously built a nest were given an initial preference test between materials of 2 *** observers then watched live-stream footage of a familiar demonstrator building a nest with material of the color that the observer did not *** this experience,observers were given the chance to build a nest with materials of the 2 *** two-thirds of the observer males preferred material of the demonstrated color after viewing the demonstrator build a nest with material of that color more than they had previously,their preference for the demonstrated material was not as strong as that of observers that had viewed live demonstrator builders in a previous *** results suggest researchers should proceed with caution before using video demonstration in tests of social learning.

关键词： construction behavior copying nest social learning video playback zebra finch

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Initial impacts of rain gardens＇ application on water quality and quantity in combined sewer： field-scale experiment

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Frontiers of Environmental Science & Engineering 2017年第4期11卷 127-138页

作者： Isam Alyaseri Jianpeng Zhou susan m. morgan Andrew Bartlett Department of Civil Engineering Al-Muthanna University Alsamawah Al-Muthanna 72001 Iraq Department of Civil Engineering Southern Illinois University Edwardsville Edwardsville IL 62026 USA Graduate School Southern Illinois University Edwardsville Edwardsville IL 62026 USA Agricultural Statistics Laboratory University of Arkansas Fayetteville AR 72701 USA

Green infrastructures such as rain gardens can benetit onsite reduction ot stormwater runott, leading to reduced combined sewer overflows. A pilot project was conducted to evaluate the impact of rain gardens on the water quality and volume reduction of storm runoff from urban streets in a combined sewer area. The study took place in a six-block area on South Grand Boulevard in St. Louis, missouri. The impact was assessed through a comparison between the pre-construction （2011/2012） and the post-construction （2014） phases. Shortly after the rain gardens were installed, the levels of total suspended solids, chloride, total nitrogen, total phosphorous, zinc, and copper increased. The level of mercury was lower than the detection level in both phases. E. coli was the only parameter that showed statistically significant decrease following the installation of rain gardens. The likely reason for initial increase in monitored water quality parameters is that the post-construction sampling began after the rain gardens were constructed but before planting, resulted from soil erosion and wash-out from the mulch. However, the levels of most of water quality parameters decreased in the following time period during the post-construction phase. The study found 76% volume reduction of stormwater runoff following the installation of rain gardens at one of studied sites. Statistical analysis is essential on collected data because of the encountered high variability of measured flows resulted from low flow conditions in studied sewers.

关键词： Rain gardens Bioretention Combined sewer Stormwater quality and quantity

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Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

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World Journal of Gastroenterology 2014年第27期20卷 8898-8909页

作者： Khaled A Jadallah susan m Kullab David S Sanders Department of Internalmedicine King Abdullah University Hospital Faculty of medicine Jordan University of Science and Technology Department of Gastroenterology and Liver Unit Royal Hallamshire Hospital Sheffield South Yorkshire S102JF United Kingdom

Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.

关键词： Constipation Irritable bowel syndrome Drug therapy Serotonergic agents Prokinetics 5-hydroxytryptamine type 4 agonists Secretagogues Prosecretory agents Bile acid modulators

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Ron receptor-dependent gene regulation of Kupffer cells during endotoxemia

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Hepatobiliary & Pancreatic Diseases International 2014年第3期13卷 281-292页

作者： Rishikesh m Kulkarni William D Stuart susan E Waltz Department of Cancer Biology University of Cincinnati Department of Research Cincinnati Veterans Affairs Medical Center

BACKGROUND: Ron receptor tyrosine kinase signaling in macrophages, including Kupffer cells and alveolar macrophages,suppresses endotoxin-induced proinflammatory cytokine/chemokine production. Further, we have also identified genes from Ron replete and Ron deplete livers that were differentially expressed during the progression of liver inflammation associated with acute liver failure in mice by microarray *** important genes and signaling pathways have been identified downstream of Ron signaling during progression of inflammation by this approach, the precise role that Ron receptor plays in regulating the transcriptional landscape in macrophages, and particular in isolated Kupffer cells, has still not been ***: Kupffer cells were isolated from wild-type(TK+/+)and Ron tyrosine kinase deficient(TK-/-) mice. Ex vivo, the cells were treated with lipopolysaccharide(LPS) in the presence or absence of the Ron ligand, hepatocyte growth factor-like protein(HGFL). microarray and qRT-PCR analyses were utilized to identify alterations in gene expression between ***: microarray analyses identified genes expressed differentially in TK+/+ and TK-/- Kupffer cells basally as well as after HGFL and LPS treatment. Interestingly, our studies identified mefv, a gene that codes for the anti-inflammatory protein pyrin, as an HGFL-stimulated Ron-dependent ***, lipocalin 2, a proinflammatory gene, which is induced by LPS, was significantly suppressed by HGFL *** results were validated by qRT-PCR studies on Kupffer cells treated with LPS and ***: The studies herein suggest a novel mechanism whereby HGFL-induced Ron receptor activation promotes the expression of anti-inflammatory genes while inhibiting genes involved in inflammation with a net effect of diminished inflammation in macrophages.

关键词： mst1R mefv Lcn2 met receptor Kupffer cells macrophages

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Understanding business William G. Nickels, James m. mcHugh, susan m. mcHugh 5th ed

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1999年

作者： William G. Nickels James m. mcHugh susan m. mcHugh

Included in an envelope a card containing the password to the web Online Learning Center.

ISBN: (纸本)025621980X

Included in an envelope a card containing the password to the web Online Learning Center.

关键词： Industrial management

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Phylogenetic relationships of native and introduced Bemisia tabaci (Homoptera:Aleyrodidae) from China and India based on mtCOI DNA sequencing and host plant comparisons

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Progress in Natural Science:materials International 2007年第6期17卷 645-654页

作者： susan A.Coats Ali m.Idris Judith K.Brown Department of Plant Sciences The University of ArizonaTucsonAZ 85721USA

Phylogenetic relationships for Bemisia tabaci were reconstructed by analysis of a ～780 bp fragment of the mitochondrial cytochrome oxidase I (mtCOI) gene with an emphasis on geographic range and distribution among eight eudicot plant families that are common hosts of B. tabaci worldwide to elucidate key phylogeographic linkages between populations extant in China (n=31) and India (n=34). Bootstrap values for the maximum Parsimony tree were highly robust for all major nodes involving the major Asian clade, subgroups, and sister groups within, at 92%—100%. Between-clade distances for the Southeast Asia and three other major clades, e.g. from sub-Sahara Africa, North Africa-mediterranean, and the Americas, were approximately >16% divergent. Two major Asian subgroups (I, II) were resolved, which represented populations indigenous to the region, comprising two (I a, I b) and five (II a—e) sister groups, respectively, which diverged by 11%. Two distinct populations from sunflower in Hyderabad grouped separately within the two Asian subgroups. All other populations grouped uniquely within Asian subgroup II or I. The "B" biotype was identified in 23 collections from China at 97.3%—99.5% nucleotide identity with "B" biotype reference sequences; it was not identified in collections from India. The majority of haplotypes were associated with 3—4 plant families, with one exception that for sister group IId (sesame, India), it might be monophagous. Thus, B. tabaci from the southeastern and near eastern regions of the Asian continent comprise of a large number of ancestral, richly divergent, mostly polyphagous populations. This region is therefore hypothesized to constitute an important Old World center of diversification for the B. tabaci complex, together with sub-Saharan Africa.

关键词： Bemisia tabaci complex cytochrome oxidase I host range phylogenetic relationship

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